Contribution of voltage-dependent K⁺ channels to metabolic control of coronary blood flow

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• 作者：Zachary C. Berwick^a ; Gregory M. Dick^b ; Steven P. Moberly^a ; Meredith C. Kohr^a ; Michael Sturek^a ; Johnathan D. Tune^a ; ^{jtune@iupui.edu}
• 关键词：(MetS) ; metabolic syndrome ; (KV) ; voltage-activated potassium channels ; (4-AP) ; 4-aminopyridine ; (MVO2) ; myocardial oxygen consumption
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2012
• 期刊代码：171_00222828
• 类别：bio
• 出版时间：April, 2012
• 卷：52
• 期：4
• 页码：912-919
• 文件大小：437 K

摘要

The purpose of this investigation was to test the hypothesis that K_V channels contribute to metabolic control of coronary blood flow and that decreases in K_V channel function and/or expression significantly attenuate myocardial oxygen supply-demand balance in the metabolic syndrome (MetS). Experiments were conducted in conscious, chronically instrumented Ossabaw swine fed either a normal maintenance diet or an excess calorie atherogenic diet that produces the clinical phenotype of early MetS. Data were obtained under resting conditions and during graded treadmill exercise before and after inhibition of K_V channels with 4-aminopyridine (4-AP, 0.3 mg/kg, iv). In lean-control swine, 4-AP reduced coronary blood flow ~ 15%at rest and ~ 20%during exercise. Inhibition of K_V channels also increased aortic pressure (P < 0.01) while reducing coronary venous PO₂ (P < 0.01) at a given level of myocardial oxygen consumption (MVO₂). Administration of 4-AP had no effect on coronary blood flow, aortic pressure, or coronary venous PO₂ in swine with MetS. The lack of response to 4-AP in MetS swine was associated with a ~ 20%reduction in coronary K_V current (P < 0.01) and decreased expression of K_V1.5 channels in coronary arteries (P < 0.01). Together, these data demonstrate that K_V channels play an important role in balancing myocardial oxygen delivery with metabolism at rest and during exercise-induced increases in MVO₂. Our findings also indicate that decreases in K_V channel current and expression contribute to impaired control of coronary blood flow in the MetS. This article is part of a Special Issue entitled 鈥淐oronary Blood Flow鈥?